Anterior chamber inoculation of murine cytomegalovirus (MCMV, 10(4) and 10(5) plaque-forming units) induced both physiologic and morphologic changes in the retinas of immunocompetent BALB/c and B- and T-cell-deficient severe combined immune deficient (SCID) mice. In BALB/c mice, the depression of the b-wave began on days 3-4 postinoculation (PI) and a further depression was recorded on day 7 PI. The electroretinograms (ERGs) remained depressed 1-2 weeks PI after which there was a recovery of the amplitude of the ERG 2-6 weeks later. The recovery was not complete; the maximum amplitude at 6 weeks was significantly lower than the preinoculation value. There was a greater loss in the amplitude than in the sensitivity of the ERG. Histologic examination of retinas with depressed ERGs showed swelling of the retinal pigment epithelium and distortion and shortening of the outer segment of the photoreceptors. With recovery of the ERG, there was normalization of the retinal histology. In SCID mice, the ERGs were extinguished, and there was no recovery. Histologically, there was a complete loss of the photoreceptors in the SCIDs, and electron microscopic examination showed viral particles in the retinal pigment epithelium and inner nuclear cells. These results demonstrate that MCMV can induce retinal pathology as reported in patients and show the importance of B- and T-lymphocytes in controlling the progression of this disease process.